Work in this laboratory has been focussed on the determination of three-dimensional structures of larger proteins in solution by NMR, with a particular emphasis on protein-protein, protein-ligand and protein-DNA complexes. A considerable effort has been placed on the developments of three- and four-dimensional heteronuclear NMR to extend the application of NMR as a method for determining three- dimensional structures of proteins in solution beyond the limits of conventional two-dimensional NMR (about 100 residues) to molecules in the 150- to 400- residue range. Solution structures of a number of proteins have been determined. These include the complexes of the transcription factors GAGA, Are A and HMG-I/Y with DNA, complexes of human thioredoxin with its target site from Ref and NfkB, and the DNA binding domains of the transposase and HIV-integrase-Streptococcal protein G have been investigated, and the stability and structural integrity of a number of multiple core mutants of Streptococcal protein G have been examined.